Summary

The advent of biopharmaceuticals in current medicine brought enormous benefits to the treatment of life-threatening human diseases (e.g., cancer, diabetes and neurodegenerative disorders), and improved the well-being of many people worldwide. The global portfolio of these therapeutic products include proteins and antibodies, nucleic acids, and cell-based products, and continues to expand at a rapid pace - approvals in the period 2015-2018 essentially double the typical five-yearly historical approval pace (G. Walsh, Nat. Biotechnol., 36:1136-1145, 2018) -, representing a significant share of the entire market of pharmaceuticals.

Innovation in the (bio)pharmaceutical industry has been driven towards the development of cost-effective manufacturing processes, envisaging the delivery of products in high quantity, with superior quality (purity), and high specificity, with the ultimate goal of benefiting patients. Progress in this direction have resulted from the application of novel technologies in the upstream stage (high-throughput, single-use devices, statistical optimization of media and fermentation conditions, QbD, and continuous processing), while at the downstream level, chromatography has evolved through the development of new resins and ligands, coupled with advances in process modelling, operating and control strategies.

An emerging trend is the application of alternative solvents such as ionic liquids and deep eutectic solvents, in which their structure and physicochemical properties can be tuned to address unmet needs in (bio)pharmaceutical research. These compounds may be derived from natural and reneawable sources and hold great promise in the development of efficient, sustainable and cost-effective biopharmaceuticals purification processes.

This Entry Collection aims to provide the latest progresses achieved in pharmaceuticals bioprocessing. We welcome submissions of original research, comprehensive reviews and perspectives, including, but not limited, to the following fields:

- Upstream processing (genetic engineering, systems biology, difficult-to-express proteins, expression conditions, Quality by Design approaches, process analytical technologies);

- Chromatographic purification methods (process modelling and control, continuous bioprocessing, design and characterization of resins and ligands, new formats);

- Alternative purification methods (aqueous biphasic systems, filtration, crystallization, precipitation);

- Application of neoteric solvents in upstream and downstream stages;

- Analytical characterization of biopharmaceuticals (stability, post-translational modifications, biological activity, immunogenicity); 

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Entries
Topic Review
Synthetic Biology towards Flavonoid Pharmacokinetics
Flavonoids are a structurally diverse class of natural products that have been found to have a range of beneficial activities in humans. However, the clinical utilisation of these molecules has been limited due to their low solubility, chemical stability, bioavailability and extensive intestinal metabolism in vivo. Recently, the view has been formed that site-specific modification of flavonoids by methylation and/or glycosylation, processes that occur in plants endogenously, can be used to improve and adapt their biophysical and pharmacokinetic properties. The traditional source of flavonoids and their modified forms is from plants and is limited due to the low amounts present in biomass, intrinsic to the nature of secondary metabolite biosynthesis. Access to greater amounts of flavonoids, and understanding of the impact of modifications, requires a rethink in terms of production, more specifically towards the adoption of plant biosynthetic pathways into ex planta synthesis approaches. Advances in synthetic biology and metabolic engineering, aided by protein engineering and machine learning methods, offer attractive and exciting avenues for ex planta flavonoid synthesis.
  • 2.0K
  • 04 Jun 2021
Topic Review
Plant-Based Biosynthesis of Copper/Copper Nanoparticles
Plants produce numerous secondary metabolites and rich in phytochemicals, which are potential bioresources for synthesizing Cu and CuO Nanoparticles (NPs). This green synthesis approach is environmentally friendly and more advantageous over commercial synthesis using physical and chemical methods. The green synthesized Cu and CuO NPs can be used as anticancer, antibacterial, antifungal and anti-inflammatory agents in biomedical applications. We discuss about the green synthesis of Cu and CuO NPs using various plants, factors affecting the synthesis, biomedical applications, and toxicity evaluation of the NPs. In addition, the mechanisms of the NPs entry into biological entities were also discussed. 
  • 3.3K
  • 01 Jun 2021
Topic Review
Bacterial Resistance to Antimicrobial Agents
Bacterial pathogens as causative agents of infection constitute an alarming concern in the public health sector. In particular, bacteria with resistance to multiple antimicrobial agents can confound chemotherapeutic efficacy towards infectious diseases. Multidrug-resistant bacteria harbor various molecular and cellular mechanisms for antimicrobial resistance. These antimicrobial resistance mechanisms include active antimicrobial efflux, reduced drug entry into cells of pathogens, enzymatic metabolism of antimicrobial agents to inactive products, biofilm formation, altered drug targets, and protection of antimicrobial targets. These microbial systems represent suitable focuses for investigation to establish the means for their circumvention and to reestablish therapeutic effectiveness.
  • 2.9K
  • 01 Aug 2022
Topic Review
Natural Compounds in Glioblastoma Therapy
Glioblastoma (GBM) is a tumor of the brain or spinal cord with poor clinical prognosis. Current interventions, such as chemotherapy and surgical tumor resection, are constrained by tumor invasion and cancer drug resistance. Dietary natural substances are therefore evaluated for their potential as agents in GBM treatment. Various substances found in fruits, vegetables, and other natural products restrict tumor growth and induce GBM cell death. These preclinical effects are promising but remain constrained by natural substances’ varying pharmacological properties. While many of the reviewed substances are available as over-the-counter supplements, their anti-GBM efficacy should be corroborated by clinical trials moving forward. 
  • 1.8K
  • 23 Jun 2021
Topic Review
The (Poly)Pharmacology of Cannabidiol
Cannabidiol (CBD), the major nonpsychoactive Cannabis constituent, has been proposed for the treatment of a wide panel of neurological and neuropsychiatric disorders, including anxiety, schizophrenia, epilepsy and drug addiction due to the ability of its versatile scaffold to interact with diverse molecular targets that are not restricted to the endocannabinoid system. 
  • 1.3K
  • 25 May 2021
Topic Review
Medicinal Plants with Anti-Leukemic Effects
Leukemia is a leukocyte cancer that is characterized by anarchic growth of immature immune cells in the bone marrow, blood and spleen. There are many forms of leukemia, and the best course of therapy and the chance of a patient’s survival depend on the type of leukemic disease. Different forms of drugs have been used to treat leukemia. Due to the adverse effects associated with such therapies and drug resistance, the search for safer and more effective drugs remains one of the most challenging areas of research. Thus, new therapeutic approaches are important to improving outcomes. Almost half of the drugs utilized nowadays in treating cancer are from natural products and their derivatives. Medicinal plants have proven to be an effective natural source of anti-leukemic drugs. The cytotoxicity and the mechanisms underlying the toxicity of these plants to leukemic cells and their isolated compounds were investigated.
  • 1.6K
  • 18 May 2021
Topic Review
Nutraceuticals
Nutraceuticals are essential food constituents that provide nutritional benefits as well as medicinal effects. The benefits of these foods are due to the presence of active compounds such as carotenoids, collagen hydrolysate, and dietary fibers.
  • 11.1K
  • 18 May 2021
Topic Review
Vitamin K and Age-Associated Diseases
Vitamin K is a vital cofactor in activating several proteins, which act against age-related syndromes. Thus, vitamin K can carboxylate osteocalcin (a protein capable of transporting and fixing calcium in bone), activate matrix Gla protein (an inhibitor of vascular calcification and cardiovascular events) and carboxylate Gas6 protein (involved in brain physiology and a cognitive decline and neurodegenerative disease inhibitor). By improving insulin sensitivity, vitamin K lowers diabetes risk. It also exerts antiproliferative, proapoptotic, autophagic effects and has been associated with a reduced risk of cancer. Recent research shows that protein S, another vitamin K-dependent protein, can prevent the cytokine storm observed in COVID-19 cases. The reduced activation of protein S due to the pneumonia-induced vitamin K depletion was correlated with higher thrombogenicity and possibly fatal outcomes in COVID-19 patients.
  • 1.4K
  • 16 May 2021
Topic Review
Health-Promoting Effects of Mango Fruit
Mango (Mangifera indica L.), known as the king of fruits, has an attractive taste and fragrance and high nutritional value. Mango is commercially important in India, where ~55% of the global crop is produced. The fruit has three main parts: pulp, peel, and kernel. The pulp is the most-consumed part, while the peel and kernel are usually discarded. Mango pulp is a source of a variety of reducing sugars, amino acids, aromatic compounds, and functional compounds, such as pectin, vitamins, anthocyanins, and polyphenols. 
  • 2.2K
  • 19 May 2021
Topic Review
Juglans regia L. Pellicle Extract
The difficulty to treat resistant strains-related hospital-acquired infections (HAIs) promoted the study of phytoextracts, known sources of bioactive molecules. Accordingly, in the present study, the pharmacological activities of Juglans regia (L.) pellicle extract (WPE) were investigated. The antiviral effect was tested against Herpes simplex virus type 1 and 2, Poliovirus 1, Adenovirus 2, Echovirus 9, Coxsackievirus B1 through the plaque reduction assay. The antibacterial and antifungal activities were evaluated against medically important strains, by the microdilution method.
  • 922
  • 23 Jun 2021
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